10.1021/acsomega.8b01754.s001
Feng Cao
Feng
Cao
Cari Orth
Cari
Orth
Maureen J. Donlin
Maureen
J. Donlin
Patrick Adegboyega
Patrick
Adegboyega
Marvin J. Meyers
Marvin J.
Meyers
Ryan P. Murelli
Ryan P.
Murelli
Mohamed Elagawany
Mohamed
Elagawany
Bahaa Elgendy
Bahaa
Elgendy
John E. Tavis
John
E. Tavis
Synthesis and Evaluation of Troponoids as a New Class
of Antibiotics
American Chemical Society
2018
CC 50
18 methicillin-resistant S
Antibiotics Novel antibiotics
MDR-A
Acinetobacter baumannii
anti-bacterial activity
MIC 80
New Class
MIC 80 values
α- HT
92 troponoids
Preliminary hits
Escherichia coli
reference strain
tropolone
novel troponoid antibiotics
Staphylococcus aureus
hepatoma cells
MRSA
Pseudomonas aeruginosa
combat MDR
2018-11-08 18:37:45
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Synthesis_and_Evaluation_of_Troponoids_as_a_New_Class_of_Antibiotics/7316306
Novel antibiotics
are urgently needed. The troponoids [tropones,
tropolones, and α-hydroxytropolones (α-HT)] can have anti-bacterial
activity. We synthesized or purchased 92 troponoids and evaluated
their antibacterial activities against Staphylococcus
aureus, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. Preliminary hits were assessed
for minimum inhibitory concentrations (MIC<sub>80</sub>) and cytotoxicity
(CC<sub>50</sub>) against human hepatoma cells. Sixteen troponoids
inhibited S. aureus/E. coli/A. baumannii growth by ≥80% growth at <30 μM with CC<sub>50</sub> values >50 μM. Two selected tropolones (<b>63</b> and <b>285</b>) inhibited 18 methicillin-resistant S.
aureus (MRSA) strains with similar MIC<sub>80</sub> values as against a reference strain. Two selected thiotropolones
(<b>284</b> and <b>363</b>) inhibited multidrug-resistant
(MDR) E. coli with MIC<sub>80</sub> ≤30 μM. One α-HT (<b>261</b>) inhibited
MDR-A. baumannii with MIC<sub>80</sub> ≤30 μM. This study opens new avenues for development
of novel troponoid antibiotics to address the critical need to combat
MDR bacterial infections.